As integral components of all the plasma lipoproteins, phospholipids play a central role in maintaining their structure and function. The actions of lecithin:cholesterol acyl transferase (LCAT), the major enzyme in plasma responsible for cholesterol ester formation and phospholipase A, generate large amounts of lysolecithin; the metabolic fate and clinical implications of the accumulation of this potent cytolytic substance, however, in the plasma is not known. This proposal deals with the further characterization of a new plasma enzyme, lysolecithin acyl transferase (LAT) associated with high-density lipoproteins (HDL) and requiring low-density lipoproteins (LDL) for its activity, which was demonstrated for the first time two years ago by the principal investigator. In preliminary studies, we have found that the same plasma protein mediates both LAT and LCAT activities. Not only do we wish to corroborate this new observation, but in addition we plan to examine its substrate specificity, mechanism of action, and the effects of various apoproteins on its action(s). These include the study of LDL itself as a possible binding surface for the lysolecithin acylation reaction, and as an acyl donor for lecithin formation using LDL into which isotopically-labelled lipids have been incorporated. The physiological role of LDL in lysolecithin metabolism and the clinical significance of LAT will be investigated in studies with plasma from patients with abetalipoproteinemia and hyperlipidemia. The metabolism of lysolecithin associated with specific plasma fractions will be studied in detail in order to better understand the physiological significance of LAT. The disposition of lecithin synthesized by the LAT reaction also will be studied in order to determine if it is reutilized directly in the LCAT reaction or serves a structural function in maintaining the integrity of the lipoproteins involved in its action.